Nociceptin (the same substance as orphanin FQ) is a peptide comprising 17 amino acid units having a similar structure to that of opioid peptide. Nociceptin has an augmenting activity on reaction against nociceptive stimulation, an appetite stimulating activity, an activity for reducing a space learning ability, an antagonism against an analgesic action of classic opiate agonists, a dopamine release inhibitory action, a water diuresis action, a vasodilative action and a systemic blood pressure-lowering action, and it is considered to take part in intracerebral controlling of pain, appetite and memory learning through the nociceptin receptor ORL1 [see Nature, Vol. 377, 532 (1995); Society for Neuroscience, Vol. 22, 455 (1996); NeuroReport, Vol. 8, 423 (1997); Eur. J. Neuroscience, Vol. 9, 194 (1997); Neuroscience, Vol. 75, 1 (1996); ibid., 333 (1996); Life Science, Vol. 60, PL15 (1997); ibid., PL141 (1997); Proceedings for National Academy of Sciences, Vol. 94, 14858 (1997)].
Further, it is known that morphine tolerance is reduced or memory and learning ability is improved in knockout mice in which expression of nociceptin receptor ORL1 is inhibited [see Neuroscience Letters, Vol. 237, 136 (1997); Nature, Vol. 394, 577 (1998)].
It has also been reported that nociceptin itself induces symptoms resembling withdrawal symptoms observed in morphine withdrawal, and that a non-peptide nociceptin receptor antagonist improves morphine tolerance, dependence and symptoms resembling withdrawal symptoms [see Psychopharmacology, Vol. 151, 344-350 (2000); Journal of Neuroscience, Vol. 20, 7640 (2000)].
On the other hand, nociceptin protein precursor-defective mice are reported to show behaviors resembling anxiety and changes in stress response [see Proceedings for National Academy of Sciences, Vol. 96, 10444 (1999)].
Hence the substances which specifically inhibit binding of nociceptin to the nociceptin receptor ORL1 are useful as an analgesic against diseases accompanied with pains such as cancerous pain, postoperative pain, migraine, gout, chronic rheumatism, chronic pain and neuralgia; a reliever against tolerance to narcotic analgesic such as morphine; a reliever against dependence on or addiction to narcotic analgesic such as morphine; an analgesic enhancer; an antiobesitic or appetite suppressor; a treating or prophylactic agent for learning and memory impairment or dementia in aging, cerebrovascular diseases and Alzheimer's disease; an agent for treating developmental cognitive abnormality such as attention deficit hyperactivity disorder and learning disability; a remedy for schizophrenia; an agent for treating neurodegenerative diseases such as typically Parkinsonism and chorea; an anti-depressant or treating agent for affective disorder; a treating or prophylactic agent for diabetes insipidus; a treating or prophylactic agent for polyuria; a remedy for hypotension, etc.
JP-A 6-73014 discloses pyrazole compounds similar to the compounds of the invention as a cannabinoid receptor ligand. WO2003/40107 discloses imidazole compounds similar to the compounds of the invention. However, the compounds concretely disclosed in these descriptions have an alkyl phenyl as the part of R3 in a formula (I) in the present invention; but in the invention, R3 should not be a phenyl group; and therefore, the compounds differ from those in the present invention.    Patent Reference 1: JP-A 6-73014    Patent Reference 2: WO2003/40107